Slimy, disgusting and useful

Medical researchersconduct cancer research on
a primitive fish, and make astonishing finds.

Photo: Department
of Laboratory Medicine

The hagfish dwells in the cold depths and pitch black darkness at the
bottom of the sea. It burrows in the mud and waits, nearly invisible,
for the dying and dead fish that are its food. Fishing nets with their
imprisoned fish provide a particularly appetizing feast for this mud dweller.
And if you disturb it, it sends out a great cloud of sticky slime.

This jawless slimy creature may be revolting, but don’t be too
disgusted: hagfish are our distant relatives.

Mysterious reproduction
“The hagfish belongs to the roundmouth family, and lies on the same
evolutionary line as humans”, says Professor Emeritus Sture Falkmer
at the Department of Laboratory Medicine, Children’s and Women’s
Health at NTNU. “The species has been around for 500 million years,
and was among the first that developed something that was the beginning
of a vertebral column. Its other anatomical structures are also quite
‘primitive’, but are also found among the higher vertebrates”.
Falkmer says the hagfish’s unusual features have interested scientists
since the 18th century. Early research pioneers were all Scandinavian;
among the most famous was Fridtjof Nansen. Yet much about the hagfish
remains to be discovered, he said. For example, it’s still a mystery
how the hagfish reproduces.

“One hundred and fifty years ago, the Royal Danish Academy of
Sciences and Lettersannounced an award to anyone who could uncover the
secret”, Falkmer said. “The award has not yet been claimed”.

“A pea-sized lump”
Falkmer has studied this strange creature since the 1960s, when he was
fresh out of medical school. His first encounters were as a result of
diabetes research at the University of Uppsala. The project involved studying
the production of insulin, which takes place in a group of pancreatic
cells known as the islets of Langerhans. Falkmer and his colleagues studied
these cells, first in vertebrate fish and later in hagfish, and compared
their findings with the condition in humans. Along the way they made surprising
and remarkable findings.

Hagfish produce insulin in a tiny organ called the islet organ, which
lies on the wall of the bile duct where it opens into the bowels. This
insulin is the most primitive of all known. Researchers eager to conduct
biochemical analyses on this kind of insulin had to collect samples from
tens of thousands of hagfish to come up with just one gram of insulin.

“As we were doing this, we noticed that some of the hagfish had
strange knots in their livers. Some were the size of a pinhead, others
the size of a pea. Closer examination revealed them to be tumours, mostly
liver cancer”, Falkmer said. “For the first time ever it was
scientifically established that even primitive species can develop cancer”.

Poisoned food
The finding led to a systematic investigation. Researchers subsequently
detected cancer of the liver or the insulin-producing organ in between
one and eight out of every hundred hagfish, a cancer rate far higher than
had ever been measured before in animals or humans. The hagfish were caught
near the mouth of the Gullmar fjord in Sweden, and out in open sea. Every
single hagfish that had cancer had been caught in the Gullmar fjord. As
the investigation continued into the early 1970s, researchers found yet
another surprise: the number of tumours had dropped dramatically. Eventually
the tumours disappeared.

But why? Falkmer thinks he knows the reason. During the course of the
investigation, sewage treatment plants were built in the Gullmar fjord,
and Sweden banned the use of chlorinated pesticides and chemicals such
as DDT and PCBs.

“The hagfish is a bottom dwelling scavenger”, Falkmer said.
“It is easy to conclude that they developed cancer from eating fish
that had died as a result of pollution”.

Modern-day canary
The link between liver cancer and pollution is one that is highly debated.
Hagfish, like humans, feed at the top of the food chain. Falkmer thinks
that makes hagfish a good indicator of pollution levels in the sea. He
sees the hagfish as a kind of modern-day canary in a coal mine. Just as
canaries were used by miners to detect toxic gases in mine shafts, hagfish
could be used to detect carcinogenic substances in the environment, Falkmer
says.

Primary liver cancer in humans is uncommon in Western Europe, but is
relatively common in Africa and China. Falkmer said his work with hagfish
makes him think that polluted food may be part of the problem.

“This relationship has been explained by geographical differences
in nutrition and infection rates”, he said. “That liver cancer
is common in animals eating polluted food strengthens the hypothesis that
bad food could be one of several reasons for this disease”.

Eating your research subjects
Falkmer and his research colleague Kåre Emil Tvedt at NTNU have
studied digestion and hydrochloric acid production in hagfish. Kidney
researchers have looked to unlock the secrets of human kidney development
by studying its primitive relative in the hagfish. Neuroanatomists have
studied its brain.

“Organ development in earlier stages of evolution can tell us something
about our situation today”, Falkmer says. “We need to see
how anatomical structures and physiological functions work, even in their
most primitive forms. The demands on an organism to survive makes for
constant development and change”, Falkmer says.

Even after 50 years of research, Falkmer is still fascinated by the hagfish.
He’s even eaten his research subjects, once as a casserole, with
a garnish of hagfish eggs. “Not particularly tasty”, he admits.
Hagfish may taste bad, but their skin is durable and strong. Falkmer even
has a wallet made from the stuff.

Gooey,
but predator-free

The hagfish’s Latin name, Myxine glutinosa,
comes from the Greek myxa, meaning mucus, and the Latin gluten,
meaning glue. The name underlines the hagfish’s unique ability
to respond to stress by quickly extruding a thick, protective layer
of slime around its body. It can tie itself in knots and squirm
free of this gooey cloud to avoid suffocating in its own slime.
Researchers think this characteristic means that the hagfish probably
has very few enemies. If a predatory fish decides to try to eat
a hagfish, it will find itself with a mouth full of -slime.

Chewing the slime causes it to expand, eventually
asphyxiating the fish. The slime is actually ‘armed’
with fibres half a meter long. Each fibre is just a thousandth of
a millimetre thick, but very strong. Researchers have been trying
for years to unlock the secrets of exactly how the slime fibres
are put together. The answer could lead to new synthetic materials
with great strength.

The hagfish dwells in most Norwegian fjords
and can grow to be 40 centimetres long and as thick as a thumb.
Related species can be found in all the world’s oceans where
the water is at least 20 meters deep and the bottom is muddy.

The hagfish was first described by the Swede
Per Kalm in “En resa till Norra America” (A Journey
to Northern America) in 1753. Kalm began the journey from Uppsala
in 1747, travelling at the request of Carl von Linné. Boat
repairs delayed the party in Grimstad at the very beginning of the
trip. Kalm discovered the hagfish during the delay, but thought
it was a blind lamprey. He wrote down his observations, and shared
them with Linné. Linné corresponded with the Norwegian
Bishop and naturalist Johan Ernst Gunnerus about this strange creature.
Gunnerus first wrote about the hagfish in 1763, calling it a Sleep-Marken.
Both Gunnerus and Linné classified the hagfish as a worm.
But in 1790-1792, however, it was found to be its own species in
the roundmouth family under the name Myxine glutinosa.